Biermann Riekje, Rösner Laura, Beyer Lisa-Marie, Niemeyer Laura, Beutel Sascha
Institute of Technical Chemistry Leibniz University Hannover Hannover Germany.
Eng Life Sci. 2023 Sep 15;23(10):e2300210. doi: 10.1002/elsc.202300210. eCollection 2023 Oct.
is a promising probiotic, because it combines probiotic properties of and the ability of to form endospores. Due to this hybrid relationship, cultivation of this organism is challenging. As the probiotics market continues to grow, there is a new focus on the production of these microorganisms. In this work, a strain-specific bioprocess for was developed to support growth on one hand and ensure sporulation on the other hand. This circumstance is not trivial, since these two metabolic states are contrary. The developed bioprocess uses a modified chemically defined medium which was further investigated in a one-factor-at-a-time assay after adaptation. A transfer from the shake flask to the bioreactor was successfully demonstrated in the scope of this work. The investigated process parameters included temperature, agitation and pH-control. Especially the pH-control improved the sporulation in the bioreactor when compared to shake flasks. The bioprocess resulted in a sporulation efficiency of 80%-90%. This corresponds to a sevenfold increase in sporulation efficiency due to a transfer to the bioreactor with pH-control. Additionally, a design of experiment (DoE) was conducted to test the robustness of the bioprocess. This experiment validated the beforementioned sporulation efficiency for the developed bioprocess. Afterwards the bioprocess was then scaled up from a 1 L scale to a 10 L bioreactor scale. A comparable sporulation efficiency of 80% as in the small scale was achieved. The developed bioprocess facilitates the upscaling and application to an industrial scale, and can thus help meet the increasing market for probiotics.
是一种很有前景的益生菌,因为它兼具[具体菌种1]的益生菌特性以及[具体菌种2]形成内生孢子的能力。由于这种混合关系,该微生物的培养具有挑战性。随着益生菌市场持续增长,对这些微生物的生产有了新的关注焦点。在这项工作中,开发了一种针对[目标微生物]的菌株特异性生物工艺,一方面支持其生长,另一方面确保其形成孢子。这种情况并非微不足道,因为这两种代谢状态是相反的。所开发的生物工艺使用了一种改良的化学限定培养基,在适应后通过一次只改变一个因素的试验进行了进一步研究。在这项工作的范围内成功展示了从摇瓶到生物反应器的转移。所研究的工艺参数包括温度、搅拌和pH控制。特别是与摇瓶相比,pH控制提高了生物反应器中的孢子形成率。该生物工艺的孢子形成效率达到了80%-90%。这相当于由于转移到具有pH控制的生物反应器中,孢子形成效率提高了七倍。此外,还进行了实验设计(DoE)以测试该生物工艺的稳健性。该实验验证了所开发生物工艺的上述孢子形成效率。之后,该生物工艺从小规模的1升扩大到10升生物反应器规模。实现了与小规模相当的80%的孢子形成效率。所开发的生物工艺有助于扩大规模并应用于工业规模,从而有助于满足不断增长的益生菌市场需求。